U.S. patent application number 11/391981 was filed with the patent office on 2007-01-25 for combination vertical and lateral flow immunoassay device.
This patent application is currently assigned to Becton, Dickinson and Company. Invention is credited to Nicholas R. Bachur, Miroslaw Bartkowiak, P. Shawn Beaty, Alexander Clark, Timothy G. Foley, A. David Lentz, Dwight Livingston, Daniel Schwartz, Michael R. Walters.
Application Number | 20070019502 11/391981 |
Document ID | / |
Family ID | 36716838 |
Filed Date | 2007-01-25 |
United States Patent
Application |
20070019502 |
Kind Code |
A1 |
Foley; Timothy G. ; et
al. |
January 25, 2007 |
Combination vertical and lateral flow immunoassay device
Abstract
A system comprising one or more sample vessels is provided, the
sample vessels comprising a liquid growth medium and a stirrer
element, the stirrer element capable of being influenced by a
magnetic force, and an incubation and measurement module comprising
one or more openings for holding the one or more sample vessels.
The incubation and measurement module further comprises at least
two drive magnets associated with each of the sample vessels, and a
magnet driver adapted to repeatedly move each of the at least two
drive magnets toward and away from the surface of the associated
sample vessel.
Inventors: |
Foley; Timothy G.; (Forest
Hill, MD) ; Beaty; P. Shawn; (Dallastown, PA)
; Walters; Michael R.; (Baltimore, MD) ; Clark;
Alexander; (Baltimore, MD) ; Livingston; Dwight;
(Fallston, MD) ; Lentz; A. David; (York, PA)
; Bartkowiak; Miroslaw; (New Freedom, PA) ;
Schwartz; Daniel; (Timonium, MD) ; Bachur; Nicholas
R.; (Monkton, MD) |
Correspondence
Address: |
DAVID W. HIGHET, VP AND CHIEF IP COUNSEL;BECTON, DICKINSON AND COMPANY
1 BECTON DRIVE, MC 110
FRANKLIN LAKES
NJ
07417-1880
US
|
Assignee: |
Becton, Dickinson and
Company
Franklin Lakes
NJ
|
Family ID: |
36716838 |
Appl. No.: |
11/391981 |
Filed: |
March 28, 2006 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
60665692 |
Mar 28, 2005 |
|
|
|
Current U.S.
Class: |
366/273 |
Current CPC
Class: |
G01N 2035/00465
20130101; B01F 13/0818 20130101; G01N 35/00 20130101; B01F
2009/0063 20130101; B01F 9/0016 20130101; G01N 35/028 20130101 |
Class at
Publication: |
366/273 |
International
Class: |
B01F 13/08 20060101
B01F013/08 |
Claims
1. A system comprising: a plurality of sample vessels, the sample
vessels comprising a liquid growth medium and a stirrer element,
the stirrer element capable of being influenced by a magnetic
force; an incubation and measurement module comprising a plurality
of openings for holding the sample vessels, and further comprising
a number of drive magnets equal to at least twice the number of
openings, wherein each of the openings is associated with at least
two of the drive magnets; and a magnet driver comprising a
plurality of the drive magnets, adapted to repeatedly move each of
the at least two drive magnets toward and away from the surface of
an associated sample vessel when located in the associated opening,
and wherein the openings are configured to hold the sample vessels
such that the longitudinal axis of the vessels are at an angle of
less than 90.degree. with the horizontal.
2. The system of claim 1, wherein during operation of the magnet
driver, the at least two drive magnets associated with one of the
sample vessels move closest to the surface of the associated sample
vessel at different points in time, and the movement of the at
least two drive magnets imposes a magnetic influence on the stirrer
element in the associated sample vessel to move the stirrer
element.
3. The system of claim 2, wherein each of the one or more openings
are associated with a set of first and second drive magnets; and
wherein the magnet driver comprises: a magnet shaft assembly
comprising a shaft and the plurality of the drive magnets, and a
motor engaged with the shaft to rotate the magnet shaft assembly
and move the plurality of drive magnets such that the first drive
magnet is closest to the outer surface of the associated sample
vessel and the second drive magnet is away from the outer surface
of the associated sample vessel in a first rotational position, and
the second drive magnet is closest to the outer surface of the
associated sample vessel and the first drive magnet is away from
the outer surface of the associated sample vessel in a second
rotational position.
4. The system of claim 2, wherein the magnet driver comprises: a
magnet shaft assembly comprising a shaft and the plurality of the
drive magnets, wherein the plurality of drive magnets are coupled
to the shaft in pairs, the pairs being discreet components or are
discreet parts of a single component or a combination thereof,
wherein the pairs comprise a first drive magnet coupled to and
extending from the shaft at a first angle, and a second drive
magnet coupled to and extending from the shaft at a second angle,
and wherein the first drive magnet is associated with a first of
the one or more openings and the second drive magnet is associated
with a second of the one or more openings adjacent to the first of
the one or more openings.
5. The system of claim 4, wherein the first and second drive
magnets extend from first and second locations on the shaft,
respectively, and wherein the first and second locations are at
approximately opposite sides of the shaft.
6. The system of claim 3, wherein the first and second rotational
positions are approximately 180 degrees apart.
7. The system of claim 4, wherein the first and second angles are
approximately 30 degrees.
8. The system of claim 4, wherein the magnet shaft assembly is
located in the module such that each of the drive magnet pairs is
located between two of the sample vessel openings.
9. The system of claim 1, wherein upon operation of the magnet
driver, the magnetic influence moves the stirrer element along a
side wall of the sample vessel.
10. The system of claim 1, wherein upon operation of the magnet
driver, the magnetic influence moves the stirrer element in an
analemma pattern in the sample vessel.
11. The system of claim 1, wherein the magnet driver and drive
magnets are arranged such that, during a portion of the movement of
the drive magnets, gravity moves the stirrer element toward a
bottom of the sample vessel.
12. The system of claim 1, wherein the angle is about 15.degree. to
about 25.degree..
13. The system of claim 1, wherein the sample vessels are elongated
sample vials.
14. A system comprising: a plurality of sample vessels, the sample
vessels comprising a liquid growth medium and a stirrer element,
the stirrer element capable of being influenced by a magnetic
force; an incubation and measurement module comprising a plurality
of openings for holding the one or more sample vessels, wherein
each of the one or more openings is associated with at least two
drive magnets, and a magnet driver comprising a plurality of the
drive magnets adapted to repeatedly move each of the at least two
drive magnets toward and away from the surface of an associated
sample vessel when located in the associated opening, the magnet
driver comprising a magnet shaft assembly; wherein the magnet shaft
assembly comprises a shaft and a plurality of the drive magnets,
and wherein the plurality of drive magnets are coupled to the shaft
in pairs, the pairs being discrete components or discrete parts of
a single component, or a combination thereof,
15. The system of claim 14, wherein upon operation of the magnet
driver, the at least two drive magnets associated with one of the
sample vessels move closest to the surface of the associated sample
vessel at different points in time, and the movement of the at
least two drive magnets imposes a magnetic influence on the stirrer
element in the associated sample vessel to move the stirrer
element.
16. The system of claim 15, wherein the magnet driver further
comprises: a motor engaged with the shaft to rotate the magnet
shaft assembly and move the drive magnets such that a first drive
magnet is closest to the outer surface of the associated sample
vessel and a second drive magnet is away from the outer surface of
the associated sample vessel in a first rotational position, and
the second drive magnet is closest to the outer surface of the
associated sample vessel and the first drive magnet is away from
the outer surface of the associated sample vessel in a second
rotational position.
17. The system of claim 14, wherein each of the drive magnet pairs
comprises: a first drive magnet coupled to and extending from the
shaft at a first angle, and a second drive magnet coupled to and
extending from the shaft at a second angle, wherein the first drive
magnet is associated with a first of the one or more openings and
the second drive magnet is associated with a second of the one or
more openings adjacent to the first of the one or more
openings.
18. The system of claim 17, wherein the first and second drive
magnets extend from first and second locations on the shaft,
respectively, and wherein the first and second locations are at
approximately opposite sides of the shaft.
19. The system of claim 16, wherein the first and second rotational
positions are approximately 180 degrees apart.
20. The system of claim 17, wherein the first and second angles are
approximately 30 degrees.
21. The system of claim 14, wherein the magnet shaft assembly is
located in the module such that each of the drive magnet pair is
located between two of the sample vessel openings.
22. A method for stirring a sample, comprising the steps of:
providing a sample vessel comprising a liquid and a stirrer element
capable of being influenced by a magnetic force; tilting the vessel
such that the longitudinal axis of the vessel is at an angle of
less than 90.degree. with the horizontal; and providing at least
two drive magnets configured to periodically impose a magnetic
influence on the stirrer element.
23. The method of claim 22, further comprising the step of
repeatedly moving the at least two drive magnets toward and away
from an outer surface of the sample vessel.
24. The method of claim 22, further comprising the step of exerting
the magnetic influence on the stirrer element from each of the at
least two drive magnets at different points in time.
25. The method of claim 22, wherein each of the at least two drive
magnets is moved closest to the surface of the sample vessel at
different points in time.
26. The method of claim 23, wherein the step of moving comprises:
moving a first drive magnet away from the outer surface of the
sample vessel as a second drive magnet is moved toward the outer
surface of the sample vessel.
27. The method of claim 26, wherein the first and second drive
magnets move toward and away from different locations on the outer
surface of the sample vessel.
28. The method of claim 23, wherein the magnetic influence moves
the stirrer element along a side wall of the sample vessel.
29. The method of claim 23, wherein, during a portion of the
moving, gravity moves the stirrer element toward the bottom of the
sample vessel.
30. The method of claim 22, wherein the magnetic influence moves
the stirrer element in an analemma pattern.
31. The method of claim 22, wherein the stirrer element is
magnetized to between about 200 Gauss to about 400 Gauss.
32. The method of claim 31, wherein the stirrer element is
magnetized to about 300 Gauss.
Description
REFERENCE TO PRIOR APPLICATIONS
[0001] This application claims priority to U.S. Provisional Patent
Application Ser. No. 60/665,692, filed Mar. 28, 2005.
BACKGROUND OF THE INVENTION
[0002] 1. Field of the Invention
[0003] The invention relates to an improved system and method for
stirring suspended solids in a liquid media.
[0004] 2. Description of the Related Art
[0005] Many medical diagnoses require that a fluid sample, such as
a blood sample, be taken from a patient, cultured in a growth
medium, and then examined for the presence of a pathogen believed
to be causing the patient's illness. The growth medium provides
nutrients that allow the pathogen, such as bacteria, virus,
mycobacteria, mammalian cells or the like, to multiply to a
sufficient number so that their presence can be detected.
[0006] In some cases, the pathogen can multiply to a large enough
number so that it can be detected visually. For example, a portion
of the culture can be placed on a microscope slide, and visually
examined to detect for the presence of a pathogen of interest.
[0007] Alternatively, the presence of a pathogen or other organism
can be detected indirectly by detecting for the presence of
byproducts given off by the microorganism during its growth. For
example, certain microorganisms such as mammalian cells, insect
cells, bacteria, viruses, mycobacteria and fungi consume oxygen
during their growth and life cycle. As the number of microorganisms
increases in the sample culture, they naturally consume more
oxygen. Furthermore, these oxygen consuming organisms typically
release carbon dioxide as a metabolic byproduct. Accordingly, as
the number of organisms present increases, the volume of carbon
dioxide that they collectively release likewise increases.
[0008] Alternatively, instead of measuring the presence of carbon
dioxide to detect the presence of an oxygen consuming
microorganism, it is possible to measure a depletion in the
concentration of oxygen in the sample of interest. The presence of
oxygen consuming organisms can also be detected by measuring a
change in the pressure in a sealed sample vial containing the
sample of interest. That is, as oxygen in a closed sample vial is
depleted by oxygen consuming organisms, the pressure in the sealed
sample vial will change. The pressure will further change in the
sample vial as the organisms emit carbon dioxide. Therefore, the
presence of such organisms can be detected by monitoring for
changes in pressure in the closed sample vial.
[0009] Several methods exist for measuring the increase of carbon
dioxide in a sample to determine whether organisms are present in
the sample. For example, an instrument known as the Bactec.RTM.
9050 manufactured by Becton Dickinson and Company detects changes
in the color of an indicator to determine whether carbon dioxide is
present in a sample. That is, each sample is collected in a
respective sample vial containing an indicator medium having a
chemical that reacts in the presence of carbon dioxide to change
color. A light sensor then detects the color of the indicator
medium in the sample vial when the sample vial is loaded into the
instrument. If the sample contains an organism which emits carbon
dioxide as a function of growth and/or metabolic activity, the
reflected or fluorescent intensity of the indicator medium will
change in response to the presence of carbon dioxide. The light
sensor will therefore detect this change in intensity, and the
instrument will thus indicate to an operator that an organism is
present in the sample contained in the sample vial. Other examples
of instruments for detecting the presence of organisms in a sample
by measuring the changes in carbon dioxide in the sample are
described in U.S. Pat. Nos. 4,945,060, 5,164,796, 5,094,955 and
5,217,876, the entire content of each of these patents being
incorporated herein by reference.
[0010] An instrument employing an oxygen detecting technique is
described in U.S. Pat. No. 5.567,598, the entire content of which
is incorporated herein by reference. Instruments that are capable
of detecting changes in the pressure in the sample vial are
described in U.S. Pat. Nos. 4,152,213, 5,310,658, 5,856,175 and
5,863,752, the entire content of each of these patents being
incorporated herein by reference. In addition, an instrument
capable of detecting changes in carbon dioxide concentrations,
changes in oxygen concentrations, and changes in pressures in the
vessel is described in a U.S. patent application of Nicholas R.
Bachur et al. entitled "System and Method for Optically Monitoring
the Concentration of a Gas, or the Pressure, in a Sample Vial to
Detect Sample Growth", Ser. No. 09/892,061, filed on Jun. 26, 2001,
and another instrument capable of detecting changes in carbon
dioxide concentrations or changes in oxygen concentrations in the
vessel is described in a U.S. Pat. No. 6,709,857, the entire
contents of both being incorporated herein by reference.
[0011] It is noted that the results obtained by the organism
detection techniques described above can be improved if the growth
of the organism is enhanced to cause a greater production of carbon
dioxide, a greater depletion of oxygen, or a greater change in
pressure in the vessel. It is known that the biological activity of
a solid sample in a liquid media can be enhanced by maintaining the
solid sample in a suspended state. This can be accomplished by
continuously stirring the solid-liquid mixture, which improves
nutrient, waste and gas exchanges in the mixture.
[0012] Examples of stirring techniques are described in U.S. Pat.
Nos. 5,586,823, 4,483,623 and 4,040,605, the entire content of each
of these patents being incorporated herein by reference. Each of
these techniques employs a magnetic stirrer that is placed in the
vessel containing the sample and manipulated by a magnet to stir
the sample in the vessel.
[0013] Although these stirring techniques may be somewhat effective
in enhancing sample growth, a need exists for an improved system
and method for stirring suspended solids in a liquid media to
enhance sample growth and thus improve sample detection
results.
SUMMARY OF THE INVENTION
[0014] In one embodiment, a system comprising one or more sample
vessels is provided, the sample vessels comprising a liquid growth
medium and a stirrer element, the stirrer element capable of being
influenced by a magnetic force, and an incubation and measurement
module comprising one or more openings for holding the one or more
sample vessels. The incubation and measurement module further
comprises at least two drive magnets associated with each of the
sample vessels, and a magnet driver adapted to repeatedly move each
of the at least two drive magnets toward and away from the surface
of the associated sample vessel. The openings are configured to
hold the sample vessels such that the longitudinal axis of the
vessels are at an angle of less than 90.degree. with the
horizontal.
[0015] In another embodiment, a system comprising one or more
sample vessels is provided, the sample vessels comprising a liquid
growth medium and a stirrer element, the stirrer element capable of
being influenced by a magnetic force, and an incubation and
measurement module comprising one or more openings for holding the
sample vessels. The incubation and measurement module further
comprises at least two drive magnets associated with each of the
one or more sample vessels and a magnet driver comprising a magnet
shaft assembly that comprises a shaft and a plurality of the drive
magnets. The drive magnets are coupled to the shaft in -pairs, and
the magnet driver is adapted to repeatedly move each of the at
least two drive magnets toward and away from the surface of the
associated sample vessel.
[0016] In a further embodiment, a method for stirring a sample is
provided, comprising the steps of providing a sample vessel
comprising a liquid and a stirrer element capable of being
influenced by a magnetic force, tilting the vessel such that the
longitudinal axis of the vessel is at an angle of less than
90.degree. with the horizontal, and providing at least two drive
magnets configured to repeatedly impose a magnetic influence on the
stirrer element.
BRIEF DESCRIPTION OF THE DRAWINGS
[0017] FIG. 1 is a perspective view of system according to an
embodiment of the invention;
[0018] FIG. 2 is a detailed perspective view of an example of a
panel in the system shown in FIG. 1 for housing sample vessels;
[0019] FIG. 3 is a side view of the panel shown in FIG. 2;
[0020] FIG. 4 is a diagrammatic view of a belt and pulley
arrangement employed in the panel shown in FIG. 2;
[0021] FIG. 5 is a detailed exploded view of the drive arrangement
of an embodiment of the invention;
[0022] FIG. 6 is a detailed view of the motor of the drive
arrangement shown in FIG. 5;
[0023] FIG. 7 is a partial side view of a gear arrangement employed
in the panel shown in FIG. 2 in accordance with another embodiment
of the invention.
[0024] FIG. 8 is an enlarged perspective view of a row segment of
the panel shown in FIG. 2 having a drive magnet arrangement in
accordance with an embodiment of the invention;
[0025] FIG. 9 is a conceptual view showing an example of the
relationship between the position and-motion of the drive magnet
arrangement of FIG. 8;
[0026] FIG. 10 illustrates the magnetic pole configuration of a
stirrer element in accordance with another embodiment of the
invention;
[0027] FIG. 11 illustrates the magnetic pole configuration of a
stirrer element in accordance with another embodiment of the
invention;
[0028] FIG. 12 illustrates the magnetic pole configuration of a
stirrer element in accordance with another embodiment of the
invention
[0029] FIG. 13 is a conceptual view showing an example of the
stirrer motion created by the drive magnet arrangement of an
embodiment of the invention;
[0030] FIG. 14 shows a configuration of drive magnet pairs
according to an embodiment of the invention.
[0031] Identical and like reference numerals refer to identical and
like parts, components and structures.
DESCRIPTION
[0032] FIG. 1 shows an embodiment of a system including an
incubation and measurement module 100 used for stirring samples
suspended in liquid media in sample vessels 102. As illustrated,
the incubation and measurement module 100 in this example includes
a housing 104 and two panels 106 that can be slid into and out of
the housing 104 along respective rail arrangements 108 in a
direction along arrow A.
[0033] Each panel 106 includes a plurality of openings 110, each of
which is adapted to receive a sample vessel 102. As discussed in
more detail below, each vessel 102 includes a sample suspended in a
liquid media, and a stirrer element. The openings 110 are tilted
with respect to the horizontal so that the sample vessels 102
received in the openings 110 are also tilted. Generally, the
openings are configured to hold the vessels such that the
longitudinal axis of the vessels are at an angle of less than
90.degree. with the horizontal 200 (see, e.g., FIG. 9). In this
embodiment, the openings 110 are configured such that the sample
vessels 102 received in the openings 110 are tilted at about
15.degree. with the horizontal. This tilting creates a larger air
to liquid interface 202 in the sample vessels 102 as compared to
vessels in an upright position. Furthermore, the openings 110 and
hence the sample vessels 102 need not be tilted at 15.degree. with
respect to the horizontal, but rather, can be tilted at an angle
within the range of about 15.degree. to about 25.degree., with the
range of about 15.degree. to about 20.degree. being advantageous.
However, the openings 110 and the sample vessels 102 can be tilted
at any practical angle with respect to the horizontal that will
create a useful air-to-liquid interface.
[0034] The openings 110 are arranged in a plurality of rows and
columns as shown, and each panel 106 can have any practical number
of openings. For example, the openings 110 can be arranged in ten
rows and nine columns, thus totaling 90 openings 110 per panel 106.
The incubation and measurement module 100 further includes one or
more doors (not shown) for closing the housing 104 after the panels
106 have been received in the housing 104.
[0035] When a sample culture is to be analyzed by the incubation
and measurement module 100, the sample culture is placed in a
sample vessel 102, and the sample vessel 102 is loaded into a
respective opening 110 in a respective panel 106 in the incubation
and measurement module 100. The sample vessel 102 is a closed
sample vial in this example. The incubation and measurement module
100 can further include a keyboard 112, a barcode reader (not
shown), or any other suitable interface that enables a technician
to enter information pertaining to the sample into a database
stored in a memory in the incubation and measurement module 100, or
in a computer (not shown) which is remote from the module 100 and
controls the operation of the module 100. The information can
include, for example, patient information, sample type, the row and
column of the opening 110 into which the sample vessel 102 is being
loaded, and so on. The module 100 can include the type of detecting
devices as described in U.S. patent application Ser. No. 09/892,061
and U.S. Pat. No. 6,709,857 referenced above.
[0036] As shown in FIG. 2, in this embodiment, each panel 106
includes a drive assembly 114 for driving a plurality of magnet
shaft assemblies 116. The drive assembly 114 includes a drive motor
assembly 118 and a pulley arrangement comprising a drive pulley
120, shaft driving pulleys 122, idler pulleys 124 and 126, and a
serpentine belt 128 that passes around the drive pulley 120, shaft
driving pulleys 122, and idler pulleys 124 and 126 (see also FIG.
4). In another embodiment shown in FIG. 7, the drive assembly can
include a drive motor assembly 118 and a gear arrangement
comprising a drive gear 121, shaft driving gears 123, and idler
gears 125, which each engage to transfer rotary motion from the
drive motor assembly 118 to each magnet shaft assemblies. The drive
motor assembly 118 includes a drive motor 130 that is controlled
by, for example, a controller 132, such as a microcontroller or the
like. The drive shaft 134 of the drive motor 130 is typically
coupled to a magnet plate 136 as shown in detail in FIG. 6. The
magnet plate 136 includes a plurality of magnets 138, which are
generally strong magnets such as rare earth magnets. The drive
motor 130 is mounted inside the housing 104 by, for example, a
mounting bracket 140.
[0037] As shown in detail in FIGS. 2 and 5, a magnet plate 142
having a plurality of strong magnets 144 such as rare earth magnets
is coupled to drive pulley 120. The drive motor 130 is positioned
inside housing 104 so-that when its corresponding panel 106 is
fully inserted in the housing 104, magnet plate 142 aligns with or
substantially aligns with magnet plate 136. It is further noted
that the drive motor 130 and magnet plate 136 are located outside
of the rear wall 146 of the incubation chamber that is housed
inside housing 104 and receives the panels 106. Accordingly, the
magnet plate 136 and magnet plate 142 are positioned on opposite
sides of the rear wall 146 of the incubation chamber. However, the
magnets 138 and 144 on magnet plates 136 and 142 are strong enough
to magnetically couple with each other through the rear wall 146 so
that when the drive motor 130 rotates magnet plate 136, the
magnetic coupling causes the rotation of magnet plate 136 to rotate
magnet plate 142. The rotation of magnet plate 142 drives drive
pulley 120, which drives the serpentine belt 128 to drive shaft
driving pulleys 122 and idler pulleys 124 and 126. In a similar
fashion in the embodiment shown in FIG. 7, the rotation of magnet
plate 142 drives drive gear 121, which drives the meshed gears of
the drive shaft driving pulleys 123 and idler pulleys 125. It is
noted that by locating drive motor 130 outside of the incubation
chamber, the heat emitted by drive motor 130 during operation does
not influence the temperature within the incubation chamber.
Furthermore, the drive motor 130 is not influenced by the heat of
the incubation chamber, which can damage the drive motor 130.
[0038] In this embodiment, each of the shaft driving pulleys 122 is
coupled to a respective magnet shaft assembly 116. (See, e.g., FIG.
8) Each drive magnet shaft assembly 116 in this embodiment includes
a shaft 148 that is coupled at one end to a respective shaft
driving pulley 122 or gear 123, extends along the width of the
panel 104 and is rotatably coupled at its other end to a mounting
assembly. A plurality of drive magnet assemblies are coupled to
each shaft 148 and rotate in unison with the shaft 148 when the
shaft 148 is rotated about its longitudinal axis by its respective
shaft driving pulley 122 or gear 123.
[0039] In the embodiment shown in FIG. 8, each drive magnet
assembly 153-n has two strong drive magnets 155-1 and 155-2 secured
to the rotatable shaft 148, thereby placing each drive magnet 155
of each assembly 153 between a proximate and distant position from
each opening 110. In this embodiment, the total number of drive
magnets 155 of a magnet shaft assembly 116 equals twice the number
of openings 110 in the row corresponding to that magnet shaft
assembly 116.
[0040] In the embodiment shown in FIGS. 8 and 9, the drive magnets
155 are provided between each of the openings 110, such that two
drive magnets engage or associate with each opening (e.g., engage
or associate with each vessel 102 when placed into the opening).
FIG. 8 is an enlarged perspective view of a row segment of the type
of panel shown in FIG. 2. FIG. 9 is a conceptual view showing an
example of the relationship between the position and motion of a
drive magnet arrangement shown in FIG. 8 and a respective sample
vessel containing a stirrer in accordance with an embodiment of the
invention.
[0041] The positioning of the drive magnets 155 ensures that two
drive magnets engage each opening 110 at alternate periods. As
shown in greater detail in FIG. 8, the drive magnets 155 in this
embodiment are provided in pairs 153 between each of the openings
110 along the shaft 148. (At each end of the shaft 148, a single
drive magnet 155 is provided between the endmost opening (not
shown) and the shaft 148 support member (not shown) in order to
provide two drive magnets associated with each opening.) The
surface of each drive magnet 155-1 can, for example, be provided as
either an N pole or an S pole, and the surface of each drive magnet
155-2 can be provided as either an S pole or an N pole,
respectively, to engage the stirrer element present in each vessel
102 in each opening 110. The drive magnets 155-1 and 155-2 can be
discreet components or can be discreet portions of a single
mechanical component.
[0042] In this embodiment, the drive magnet pairs 153-n are coupled
to the shaft 148 such that each drive magnet 155-1 and 155-2 of
each pair 153 extends from opposite sides of the shaft 148 (e.g.,
180.degree. from one another), and at an angle from the
longitudinal axis of the shaft 148. A useful angle is approximately
30 degrees from the longitudinal axis. Each drive magnet pair 153-n
is typically coupled at the same angle along the shaft 148.
[0043] In FIGS. 8 and 9, the drive magnets 155-n of adjacent drive
magnet pairs 153-n, or assemblies (e.g., magnet assemblies 153-1
and 153-2) are oriented at the same angular position with respect
to each other about the shaft 148. That is, when the drive magnet
155-1 of magnet assembly 153-3 is positioned proximate to a
corresponding opening 110, the drive magnet 155-1 of magnet
assembly 153-2 is also positioned proximate to a corresponding
opening 110 as shown in FIG. 8. In such a position, each drive
magnet 155-1 of each assembly 153-n is positioned proximate to a
corresponding opening 110. In a similar fashion, each drive magnet
155-2 of each assembly 153-n is positioned distant from an adjacent
opening 110. As the shaft 148 rotates, the positions of each drive
magnet 155-n transitions. Typically, the sets of drive magnets
associated with a single opening/single vessel are located on the
shaft such that a rotation of 180.degree. moves one magnet from a
position closest to a vessel located in the opening, to a position
furthest from the vessel, and a second magnet from a position
furthest from the vessel to a position closest to the vessel.
[0044] This embodiment reflects use of two magnets per
opening/vessel, but any plurality of magnets will provide similar
stirring advantages. In addition, the plurality of magnets
associated with each opening/vessel may be attached to the shaft in
any manner that provides the desired influence on the magnetic
stirrer within the vessel. For example, instead of drive magnet
pairs that extend from a shaft 148 at opposite sides of the shaft,
it is possible to use magnet pairs 156-1, 156-2 that extend from
the same side of the shaft, e.g. a first magnet 156-1 of a first
drive magnet assembly 160-1 extending at an angle of 30.degree.
from the shaft, and a second magnet 156-2 extending at an angle of
150.degree. of the drive magnet assembly. In such a case, the
magnets 156-1 and 156-2 of an adjacent drive magnet assembly 160-2,
will typically extend from an opposite side of the shaft 148. See,
e.g., FIG. 14, which shows such an embodiment.
[0045] FIG. 9 shows the relationship between a drive magnet 155-1
and 155-2 of a drive magnet assembly 153-n and a sample vessel 102
that has been loaded into the opening 110, according to one
embodiment. While two drive magnets 155-n engage or associate with
each opening 110 in this embodiment, FIG. 9 only illustrates one
side of the opening 110 (i.e., one drive magnet 155-2 for the
vessel 102), and illustrates one drive magnet of an adjacent
opening 10 (i.e., one drive magnet 155-1 for an adjacent vessel
that is not shown).
[0046] As shown in FIGS. 8 and 9, as shaft 148 rotates in the
direction designated R, the drive magnet 155-2 of assembly 153-1
moves proximate to the outer surface of sample vessel 102, and its
magnetic force attracts the stirrer element, in this example, a
magnetized stirrer element 162, to pull the stirrer element 162
away from the bottom edge 164 of the sample vessel 102 upward along
the wall 166 of the sample vessel 102. (Note that drive magnet
155-1 of assembly 153-1 is intended to influence an adjacent
vessel, not the vessel shown in FIG. 9.) As the drive magnet 155-2
continues to rotate, in a direction now away from the sample vessel
102, the stirrer element 162 becomes less influenced by the
magnetic force of the drive magnet 155-2, and due to gravity falls
along the wall 166 of the sample vessel 102 toward the bottom edge
164. However, at this time, the drive magnet 155-1 of an assembly
153-n.sub.+1 on the opposite side of the vessel 102 moves proximate
to the outer surface of sample vessel 102, and its magnetic force
attracts the stirrer element 165 to rotate and pull the stirrer
element 162 away from the bottom edge 164 of the sample vessel 102
upward along the wall 166 of the sample vessel 102. As the drive
magnet 155-1 of an assembly 153-n.sub.+1 on the opposite side of
the vessel 102 continues to rotate, in a direction now away from
the sample vessel 102, the stirrer element 162 becomes less
influenced by the magnetic force of the drive magnet 155-2, and due
to gravity falls along the wall 166 of the sample vessel 102 toward
the bottom edge 164. This rotate and pull movement is repeated each
time the drive magnets 155-1 and 155-2 (of adjacent drive magnet
assemblies) moves along the outer surface of the sample vessel 102,
and is repeated for each vessel of each opening 110. The stirring
action of the stirrer element 162 advantageously follows a pattern
having an analemma-like motion as shown in FIG. 13.
[0047] The motor 130 can be rotated at a speed of, for example, 150
rotations per minute, which causes the stirrer element 162 to
travel through the stirring path described above up to 150 times
per minute. However, the motor 130 can be controlled to rotate at
any practical speed to achieve the desired stirring action.
[0048] The stirrer element 162 is typically a magnetic, ferrous
metal-filled polymer. The term "magnetic" as used herein refers to
a type of ferrous metal, such as magnetic stainless steel, that
responds to the magnetic fields of a drive magnet. The ferrous
material employed in the stirrer element does not itself have to be
a magnet, nor does it have to be magnetized. The stirrer element
can be rod shaped or cylindrical as shown, or have any other
suitable shape. The stirrer element can be cylindrical with an
overall length of about 0.500 inches to 0.750 inches, and an
overall diameter of about 0.120 to about 0.220 inches, typically
with rounded ends.
[0049] By increasing the ferrous fill content of the stirrer
element 162, the magnetic influence that the drive magnet 154 has
on the stirrer element 162 will increase. Likewise, by decreasing
the ferrous fill content of the stirrer element 162, the magnetic
influence that the drive magnet 154 has on the stirrer element 162
will decrease. Accordingly, the intensity of the stirring can be
varied by simply replacing stirrer element 162 with a stirrer
having a different ferrous fill content. Furthermore, the size and
shape of the stirrer element 162 need not be changed. Also, by
magnetizing the stirrer element 162, the magnetic influence that
the drive magnet 154 has on the stirrer element 162 can be adjusted
still further. Accordingly, the intensity of the stirring can be
varied by simply replacing stirrer element 162 with a stirrer
element having a different degree of magnetization.
[0050] In each embodiment, the drive magnets 154 and 155 can be
provided having various magnetic intensities and magnetic
orientation, for example, up to 10,000 Gauss or more. Each can also
be provided alone, or in a plurality, and have various sizes and
shapes, as magnetic and rare earth magnets are capable of being
sintered or cast into different configurations. The drive magnets
can act on each opening alone, or as an array or plurality.
Different physical motions of the stirrer element can therefore be
provided, including alternative rotations, lateral, vertical, and
so forth. Each drive magnet can also be provided having different
rates of oscillation, i.e., tens, hundreds, or even thousands of
rotations per minute.
[0051] As reflected in FIGS. 10, 11 and 12, the stirrer elements
can be provided with various shapes, sizes, magnetic and polymer
fill levels, and magnetic pole orientations. For example, the shape
of the stirrer element can be selected based on the associated
forces acting upon it. The main forces on the stirrer element that
cause its intrinsic motion within the liquid include magnetism,
gravity, buoyancy and viscosity. The magnetic force causing the
movement of the stirrer element either toward or away from (in
cases where the stirrer element is magnetized) the drive magnets
varies by the coercivity of the magnetized fill in the stirrer
element, the inherent strength of the drive magnets, and inversely
by the distance between the two. Therefore, the stirrer element can
be shaped to best take advantage of the volume shape of the liquid
in order to orient its magnetic poles (when magnetized) closer to
the drive magnets. This shape could be a planar form (rectangular
polyhedral), linear (cylindrical rod), spherical, or other more
complex shape suitable for the volume stirred and the desired vigor
of agitation. Gravity tends to pull the stirrer element towards the
center of the earth. If the stirrer element is very large with
respect to the liquid volume that it is stirring (heavy), it will
tend to fall with more force than if it is small, and thus lighter.
Also, the added inertia of a larger stirrer element mass tends to
oppose any increase in gravitational attraction. Controlling the
relative mass of the stirrer element through shape optimization can
balance the gravitational force with respect to the element's
buoyancy and the liquid's viscosity. Likewise, the stirrer
element's length to diameter ratio can either increase or decrease
the force of viscous drag within the liquid. In creating more (or
less) drag, the stirrer element is either moved less (or more)
within the liquid for a given viscosity and external applied
magnetic field. In addition, the stirrer element can be magnetized
with different pole orientations and intensities. FIGS. 10, 11 and
12 illustrate a number of magnetic pole configurations of stirrer
elements 162a, 162b and 162c, in accordance with embodiments of the
invention.
[0052] In accordance with an embodiment of the invention, the
stirrer elements 162, 162a, 162b, 162c can comprise about 20% to
about 80% of polymer by weight, with the remaining 80% to 20% of
the weight being ferrous metal or other magnetic or magnetizable
materials. However, any ratio of polymer to ferrous metal can be
used as long as it provides sufficient cohesiveness to hold the
stirrer element together and to allow sufficient responsiveness to
the drive magnet 154. The polymer material is preferably a
biologically inert polymer, such as nylon or polypropylene, which
reduces the overall surface hardness of the stirrer element, and
thus reduces potential damage to the solid sample 158 in the
suspension as well as to the sample vessel 102. In one embodiment
of the invention, the ferrous material is stainless steel, but can
be any suitable material that can respond to magnetic influence
from the drive magnet 154. The stirrer element can be further color
coded with colors such as blue, gray, red, green, orange, and so
on, to provide an indication of the type and percentage content of
the polymer and ferrous material. The stirrer element can be
provided in the sample vessel 110, or can be added to the sample
vessel 110 prior to or after adding the solid sample 158 and liquid
media 160 to the sample vessel 110.
[0053] The stirrer element can be made from a material that can be
magnetized to move in response to the rotation of the permanent
magnets of the drive magnet assemblies to induce a continuous or
pulsing movement sufficient to provide a stirring motion to the
liquid reagent in each vessel. Typically, the stirrer element has a
substantially cylindrical shape with a length and diameter
sufficient to induce the desired movement to the liquid reagent.
The stirrer element generally has a length of about 15-25 mm and
diameter of about 2-6 mm. In one preferred embodiment the stirring
bar has length of about 20 mm (0.75 inches) and diameter of about 5
mm (0.22 inches). Typically, the stirrer elements have slightly
rounded ends
[0054] In a preferred embodiment, the stirrer element is produced
from a mixture of a moldable polymer or copolymer and a
magnetizable material. An example of a suitable polymer includes a
styrene-ethylene-butylene-styrene (SEBS) copolymer, as this
copolymer is biologically inert and easily molded to the desired
shape and size. In other embodiments, the polymer component of the
stirrer element is selected from the group consisting of
polyethylene, polypropylene, polybutylene, and polystyrene.
Typically, the polymer component is a flexible thermoplastic
polymer or copolymer. The polymer or copolymer is typically
included in an amount of about 20 wt % to about 40 wt % and
preferably about 30 wt % based on the total weight of the finished
stirrer element.
[0055] The magnetizable material is typically included in the
amount of about 60 wt % to about 80 wt % and preferable about 70 wt
% based on the total weight of the finished stirrer element. The
magnetizable material is generally a ferrite compound that can be
magnetized to a suitable power to provide the necessary stirring
effect. Examples of magnetizable ferrites include Group II metal
ferrites and particularly strontium ferrite. The magnetic or
magnetizable component can be selected from the group consisting of
iron, stainless steel, and ferrite alloys. One preferred embodiment
is a mixture of 30 wt % styrene-ethylene-butylene-styrene copolymer
and 70 wt % strontium ferrite. The components are mixed together
and molded by melting and extruding as a cylindrical member and
cutting to length. Alternatively the mixture of polymer and
strontium ferrite particles can be compression molded into the
desired shape, or heated and injection molded into the desired
shape. As noted above, a particularly preferred embodiment of the
invention, the stirrer element can comprise a mixture of about 70
wt % strontium ferrite with 30 wt % SEBS polymer, and molded into
an approximately 20 mm (0.75 inches) long cylinder, approximately 5
mm (0.220 inches) in diameter, and with rounded ends. The stirrer
element can be further magnetized to saturation at approximately
300 Gauss, with two poles aligned diametrically as shown in FIGS.
11 and 12, or at the ends of the element as shown in FIG. 10. The
relatively soft SEBS polymer provides adequate compliance to avoid
damage to any particulates suspended in the liquid media, and is
biologically inert. The 70 wt % strontium ferrite supplies moderate
magnetization, persistent strength, nonreactivity, and ease of
formulation and molding.
[0056] In some embodiments, the stirrer elements are formed and
then magnetized to the desired power to provide the proper stirring
effect. The stirrer elements are magnetized to a power of about 200
Gauss to about 400 Gauss using standard magnetizing procedures. In
one preferred embodiment the stirring magnet is magnetized to a
power of about 300 Gauss. The ferrite material, such as strontium
ferrite, is able to provide a moderate magnetization with
persistent strength for the intended life of the stirrer
element.
[0057] Multiple poles can be patterned within the shape of the
stirrer element, and poles can be axially oriented, radially
oriented, circularly oriented, or designed in many other
configurations to impart the desired attractive or repellent
geometry to the stirrer. Such various magnetic pole geometries can
further achieve diverse motion of the stirrer element within the
liquid and thereby produce desired effects. In preferred
embodiments of the invention, the magnetic stirrer element is
produced with the opposite poles oriented diametrically around the
circumference of the stirrer element. In one embodiment, a stirrer
element 162a is formed with a north pole at a first end, and a
south pole at a second end f the stirrer element as shown in FIG.
10. In another embodiment, a stirrer element 162b is formed with
one north pole and one south pole at each end, where the poles
extend longitudinally along substantially the entire length of the
stirrer element with the poles alternating around the circumference
of the stirrer element as shown in FIG. 11. In yet another
embodiment, the stirrer element 162c includes two or more pairs of
opposite poles at each end where the poles alternate around the
circumference of the stirrer element and extend substantially along
the length of the stirrer element as shown in FIG. 12. In this
manner the lines of magnetic flux extend around the circumference
of the stirrer element rather than end to end as in conventional
bar magnets.
[0058] The diametrically and axially oriented poles can induce a
random, 3-dimensional movement of the stirrer element in response
to the movement of the drive magnets. The drive magnets generally
move in an orbital path with respect to the culture vessel in a
sweeping motion in a plane parallel to the longitudinal axis of the
culture vessel. The axis of the circular path of the drive magnets
is such that the drive magnets move toward and then away from the
culture vessel and the stirrer element so that the stirrer element
may exhibit an erratic and pulsating motion. The circular motion of
the drive magnets in a generally sweeping path induces a random
motion to the stirrer element. The diametrically and axially
oriented poles of the stirrer element cause the stirrer element to
rotate about its longitudinal axis and simultaneously move and
rotate about an axis generally perpendicular to the longitudinal
axis of the stirrer element thereby experiencing an analemma-like
motion to provide the stirring effect.
[0059] As shown in FIGS. 11 and 12, the magnetic poles can be
induced diametrically (axially) to produce a complex,
3-dimensional, analemma-like stirring pattern as shown in FIG. 13.
The magnetic strength of the stirring element in accordance with
this embodiment of the invention is typically sufficient to break
free from sedimented red blood cells, but not so high as to rupture
cells or resin particles.
[0060] The increase in availability of many different magnetic
materials and thermoplastic polymers with a wide range of
properties in recent years has made the molding or extrusion of
such complex stirrer element shapes described above possible.
Extensive adjustments, therefore, can be made to both the design of
the stirrer element and the drive magnets, as described in greater
detail below, in order to finely control the degree of motion
imparted to the liquid. Also, the magnetization of ferrite filled
stirrer elements as described above is easily achieved using high
strength permanent magnet fixtures, rather than electromagnetic
discharge. Therefore, permanent magnet fixtures with energy
directors easily meet production volume requirements for producing
stirrer elements.
[0061] To adjust the fill ratio of magnetic material in the above
embodiments, the magnetic material that is molded with a polymeric
matrix into the stirrer element shape can have different percentage
volumes (percent fill) and can be chosen from different materials.
A higher percentage volume fill of magnetic material will tend to
make the stirrer element more massive when the other ingredients
used in the element's manufacture are lightweight polymers. The
more mass that the stirrer element has, the more influence and
effect on stirring the force of gravity will have for the same
viscosity or viscoelasticity of the liquid being stirred, and
becomes more of a factor in its motion.
[0062] In addition to percent volume adjustments, the type of
material can be varied to adjust mass and to adjust magnetic
coercivity. For example, if the powdered metal fill in the stirrer
element is a martensitic stainless steel, it will have a much lower
magnetic moment than an element with the same percentage fill but
having a higher coercivity, such as strontium ferrite.
[0063] Not only can the type of material be selected for magnetic
force, but also for nontoxicity, such as required in the case of
using the stirrer element in biological samples. Also, the
oxidation potential for the material can be selected to suit the
application. For example, rust forming in an optically interrogated
sampler container could severely impact performance.
[0064] To adjust the polymer fill in the above embodiments, the
percent volume or mass and the type of polymer used to manufacture
the stirrer element can be selectable. A higher percentage of
polymer fill can alter the stirrer physical properties for
different application environments. For instance, if the polymer
has a low durometer value (meaning it is soft) and its percentage
increased, the amount of impact force applied to the solids
suspended in the liquid media can be decreased. As the polymer
volume becomes less and the magnetic fill becomes greater, the
element's hardness typically increases and its apparent collision
damage to suspended solids may increase.
[0065] Selecting different types of polymer can also enhance other
performance attributes. If the desired compliance of the material
is known, the inherent compatibility with the stirred, contents
becomes paramount. Some polymers are known to be toxic to metabolic
processes, and some are known to be relatively inert. In the case
of selecting a nontoxic polymer, a choice of PTFE instead of
polyurethane could determine the element's ultimate effect on
stability of the stirred liquid's contents. In certain cases, the
selection of a polymer that is chemically active, absorptive, or
destructive to agents that harm the liquid's contents may be
desirable. Including these detrimental or alternatively, beneficial
polymers in the stirrer element can be used to adjust the
performance of the container's contents.
[0066] Various embodiments of the invention provide several
advantages over the conventional stirring devices. For example,
because the tilted openings I 10 maintain the sample vessel 102 at
an with respect to the horizontal, the embodiments facilitate
maximum exposure of liquid phase to gas phase. This therefore,
provides an improved dissolved gas exchange as a function of the
angle. Furthermore, the angled orientation of the sample vessel 102
increases the probability that the drive magnets will maintain
magnetic influence over the stirrer elements. Also, the stirring
action can be gentler than in conventional methods since the path
of the stirrer element is constrained by the wall 166 of the sample
vessel. All of these improved characteristics of the stirring
system enhances the growth of the sample in the liquid media 160
and thus increases the overall carbon dioxide production, oxygen
depletion and pressure variation in the sample vessel, thereby
improving sample detection results.
[0067] Those skilled in the art will appreciate that modifications
are possible in the embodiments described herein without materially
departing from the novel teachings and advantages of this
invention. Accordingly, all such modifications are intended to be
included within the scope of this invention as defined in the
following claims.
* * * * *